1. Clonal analysis of mouse intestinal epithelial progenitors
Matthew Bjerknes, Hazel Cheng 
Gastroenterology 
Volume 116, Issue 1, Pages 7-14 (January 1999)
DOI: /S (99)
Copyright © 1999 American Gastroenterological Association Terms and Conditions

2. Fig. 1
Lineage diagram illustrating columnar (C) and mucous (M) cell production. The pluripotential stem cells (S) generate additional cell types (not shown). Big arrows leading from S to C indicate the dominant pathway. Mix is a short-lived (days) progenitor cell type capable of producing both columnar and mucous short-lived progenitors (C1 and M1, respectively). M0 and C0 are long-lived (months) mucous and columnar progenitors with mucous and columnar phenotypes, respectively. The arrowheads leading from C1 and M1 to C and M indicate potential amplification of the population by several divisions of the respective committed progenitor.
Gastroenterology  , 7-14DOI: ( /S (99) )
Copyright © 1999 American Gastroenterological Association Terms and Conditions

3. Fig. 2
Graphs showing the dynamics of mutant clones. (A) Fraction of crypts containing a mutant clone. Each point represents data from 1 animal; the line segments join sample means. (B) Fraction of villi containing a mutant clone. Many crypts supply a villus, and most crypts supply >1 villus. Therefore, it is expected that mutant clones are more frequent on villi than in crypts. (C) Fraction of villi with a mutant clone containing only mucous cells. (D) Fraction of villi with a mutant clone containing only columnar cells. (E) Fraction of villi with a mutant clone containing ≥2 cell types.
Gastroenterology  , 7-14DOI: ( /S (99) )
Copyright © 1999 American Gastroenterological Association Terms and Conditions

4. Fig. 3
Photomicrographs of mutant clones in isolated epithelium. (A) Mutant clone on a villus from an SWR mouse. There are two wild-type mucous cells (blue spots) and numerous wild-type columnar cells (pale blue). Mutant cells are brown. Mutant mucous (black arrowheads), brush (white arrowheads), and many mutant columnar cells are visible. (B) Mutant Paneth cell in an SWR crypt base. (C) Lateral view of a mutant brush cell from a clone of 4 on an SWR villus. (D and E) Clone of 2 mutant enteroendocrine cells in a crypt (only 1 cell is visible in each focal plane). (F) Clone of mutant mucous cells (arrowheads) on an SWR villus 112 days after NEU administration. Note the gaps separating the mutant cells. Wild-type mucous cells are blue. (G) Six mutant mucous cells (chain of blue cells in lower part of figure) from an F1 villus mucous clone 42 days after NEU. Wild-type cells stain brown in F1 animals. (H) Two immature mutant mucous cells in position 3 (1 in focus) and a cluster of 4 on the opposite side of an SWR crypt base 84 days after NEU. (I) Single mutant mucous cell in lower crypt from an SWR mouse 28 days after NEU. There were additional mutant mucous cells on the villus (not shown). (J) Two of 4 mutant mucous cells in an SWR crypt top 3 days after NEU. (K) SWR columnar cell clone in midvillus. Note the gaps separating mutant cells. (L) Midvillus columnar cell clone (chain of unstained cells) from an F1 mouse. Note the gaps. (M) SWR crypt with a mixed clone (containing columnar, mucous, and Paneth cells). Mutant crypt base columnar cells are evident. Note the gap separating mutant cells in the crypt base from those in the upper crypt. (N) Similar to M. Note the mutant crypt base columnar cells (arrowheads) separated by a wild-type Paneth cell. (O) Basolateral surface of an SWR crypt with 2 separate clusters of mutant cells. (P) Two stripes of mutant cells on an SWR villus generated by splitting of the column of mutant cells in the crypt (see Figure 4B and C). (Q) Flow from a homogeneously mutant crypt (black arrowhead points to crypt mouth) splitting around a wild-type crypt (white arrowhead points to crypt mouth; crypts out of the focal plane), thereby generating 2 unstained stripes on an F1 villus (see Figure 4D). (R) View of the surface epithelium (transition between crypts and villi) from an SWR mouse. Three streams of mutant cells are seen emanating from the mouth of a crypt (*). Two of the streams flow around a neighboring crypt (**, crypt mouth indicated by the dotted oval), forming two stripes on a villus (not visible). The third stream flows onto a second villus (see Figure 4D and E). (S) Branching crypt from an SWR mouse. Mutant cells are visible in only 1 of the 2 branches. (T) Branching crypt from an F1 mouse. The mutant cells (unstained) have partitioned into only 1 branch. The brown cells in the base of that branch are wild-type Paneth cells (Paneth cells are long-lived).
Gastroenterology  , 7-14DOI: ( /S (99) )
Copyright © 1999 American Gastroenterological Association Terms and Conditions

5. Fig. 4
Mechanisms generating villus clonal distribution patterns. (A) Positions of mutant mucous cells along the crypt-villus axis (filled circles) correspond to time t in the graph. The clone originates from an M0 cell in the lower crypt (represented by the horizontal line in the graph). M0 divides at times indicated by arrows, yielding an M0 and an M1 (or M) cell. M1 cells divide a variable number of times as they move up the crypt. The curves represent the paths of cells and their progeny. The relative displacement of daughter cells is probably caused, in part, by subsequent divisions of intervening cells. (B) Crypt-villus unit illustrating the cell flow discontinuity that must occur as cells flow from crypt to villus. The point of flow discontinuity occurs between two neighboring cells whose paths are indicated by the curves. (C) Top view of crypt-villus unit illustrating generation of 2 mutant stripes from a partially mutant crypt as a result of discontinuous flow as shown in B. (D) Double stripes generated by flow divergence around an adjacent crypt. Split flows encompassing >1 crypts were also observed. (E) Flow to adjacent villi from a single mutant crypt.
Gastroenterology  , 7-14DOI: ( /S (99) )
Copyright © 1999 American Gastroenterological Association Terms and Conditions